Background and Objective: Sphingosine 1-phosphate (S1P), and S1P receptor modulator fingolimod have been suggested to play important cardioprotective role in animal models of myocardial ischemia/reperfusion injuries. To understand the cardioprotective function of S1P and its mechanism in vivo, we analyzed apoptotic, inflammatory biomarkers, and myocardial fibrosis in an in vivo heterotopic rat ...

Fingolimod is a new oral administrated sphingosine 1phosphate receptor modulator, approved for treatment of multiple sclerosis (MS) patients.1,2 There is evidence that fingolimod acts by preventing lymphocyte egress from lymph nodes, spleen and thymus by antagonistic action on the sphingosine 1-phosphate receptors. These receptors regulate proliferation, differentiation, survival, chemotaxis an...

The sphingolipid analog fingolimod is known to induce apoptosis of tumor cells and lymphocytes. Its effect on neutrophils has not been investigated so far. Here, we describe a fingolimod-induced atypical cell death mechanism in human neutrophils, characterized by rapid translocation of heat shock protein 27 to the cell surface, extensive cell swelling and vacuolization, atypical chromatin stain...

BACKGROUND Cases of higher-than-expected disease activity have been reported following fingolimod discontinuation. OBJECTIVE The objective of this paper is to assess the risk of substantially higher-than-expected disease activity post-study drug discontinuation (SDD) at the individual patient level using data from the Phase III, placebo-controlled FREEDOMS and FREEDOMS II trials. METHODS Ba...

OBJECTIVE Although astrocytes participate in glial scar formation and tissue repair, dysregulation of the NFκB pathway and of nitric oxide (NO) production in these glia cells contributes to neuroinflammation and neurodegeneration. Here we investigated the role of the crosstalk between sphingosine-1-phosphate (S1P) and cytokine signaling cascades in astrocyte activation and inflammation-mediated...

Purpose The purpose of this study was to evaluate the inhibitory mechanism of fingolimod and the involvement of sphingosine-1-phosphate receptors (S1PRs) and cytokines-matrix metalloproteinases (MMPs)/MAP kinases (MAPKs) signaling in a dry eye disease (DED) mouse model. Methods Sixty-four male NOD mice (DED model) and 16 age-matched BALB/c mice were used. In a preliminary experiment, 16 NOD m...

BACKGROUND AND OBJECTIVE The long term effects of fingolimod, an oral treatment for relapsing-remitting (RR) multiple sclerosis (MS), on blood circulating B and T cell subtypes in MS patients are not completely understood. This study describes for the first time the longitudinal effects of fingolimod treatment on B and T cell subtypes. Furthermore, expression of surface molecules involved in an...

OBJECTIVE We assessed CSF levels of the light chain subunit of neurofilaments (NfL) at baseline and after fingolimod therapy or placebo in patients with relapsing-remitting multiple sclerosis (RRMS). Changes in NfL levels were also correlated with relapse and MRI outcomes. METHODS CSF samples were available, at baseline and 12 months after treatment initiation, from a subset of 36 patients wi...

Fingolimod is an oral sphingosine-1-phospate (S1P) receptor modulator for the treatment of relapsing-remitting multiple sclerosis (RRMS). In addition to therapeutic effects on lymphoid and neural tissue, fingolimod influences cardiovascular system by specific S1P-receptor modulation. The effects of S1P-receptor modulation on the endogenous circadian pattern of cardiac autonomic regulation (CAR)...

BACKGROUND Adherence to disease-modifying therapies (DMTs) results in the reduction of the number and severity of relapses and delays the progression of multiple sclerosis (MS). Patients with lower adherence rates experience more inpatient visits and higher MS-related medical costs. Fingolimod, the first oral DMT approved by the US Food and Drug Administration, may improve the access and compli...